The isolated canine brain preparation is to be used to study: (a) Intermediary metabolism of carbohydrates, ketone bodies, amino acids and lipids (b) Unidirectional transport of carbohydrates, ketone bodies, TCA cycle intermediates and lipids and (c) Autoregulation of cerebral blood flow and the cerebral vascular response to vasoactive drugs. (a) Intermediary metabolism of various metabolites will be studied by adding the radioactively labeled compound to the perfusion blood and following the label distribution with time in both brain and blood carbohydrates, ketone bodies, lipids, amino acids, proteins and CO2. Brain urea synthesis will be studied with NH15 plus 4 or N15 glutamine as the precursor to elucidate the metabolic pathway used for its synthesis in the brain. (b) Using an indicator dilution technique with Na 22 as the intravascular indicator, kinetic studies of unidirectional transport of various H3 and C14 labeled carbohydrates, ketone bodies and lipids will be made in the presence and absence of inhibitors. (c) Arterial pH, PO2, PCO2 and blood pressure will be varied separately, but in increments, to quantify the effects of metabolic and myogenic factors which may cause the changes in cerebral vascular resistance that are attributed to autoregulation. Various vasoactive drugs will be injected over a range of concentrations to obtain dose response curves and to correlate structure with vascular response.